[Dryness-alleviating effect of processed Aurantii Fructus from Lingnan based on correlation of fecal metabolomics and dryness].

With the approach of untargeted metabolomics and correlation analysis, this study aimed to explore the mechanism of Aurantii Fructus from Lingnan region in alleviating dryness by analyzing the different effects of raw Aurantii Fructus(RAF) and processed Aurantii Fructus(PAF) on fecal endogenous metabolism in normal rats. Eighteen Sprague-Dawley(SD) rats were randomly divided into a control group(C), an RAF group(10 g·kg~(-1)), and a PAF group(10 g·kg~(-1)). After seven days of administration, the effects of RAF and PAF on dryness-related indexes were compared, including water intake, fecal water content, salivary secretion, the expression of AQP5, VIP, and 5-HT in the submandibular gland, as well as the expression of AQP3, VIP, and 5-HT in the colon. The fecal samples in each group were determined by LC-MS. Multivariate statistical analysis and Pearson correlation coefficient were used for screening the differential metabolites and metabolic pathways in alleviating dryness of RAF. The results indicated that both RAF and PAF showed certain dryness, and the dryness of RAF was more significant. Moreover, PAF could alleviate dryness of RAF to a certain extent by reducing the water intake, fecal water content, and the expression of AQP3, VIP, and 5-HT in the colon and increasing the salivary secretion and the levels of AQP5, VIP, and 5-HT in the submandibular gland. According to the analysis of fecal metabolomics, 99 and 58 metabolites related to dryness were found in RAF and PAF respectively, where 16 of them played an important role in alleviating dryness of RAF. Pathway analysis revealed that the mechanism of PAF in alleviating dryness of RAF was presumably related to the regulation of riboflavin metabolism, purine metabolism, arginine biosynthesis, pyrimidine metabolism, alanine metabolism, aspartate metabolism, glutamate metabolism, and retinol metabolism pathways. This study suggested that PAF might alleviate dryness of RAF by affecting the metabolic levels of the body, which provides a new basis for further clarifying the processing mechanism of PAF.

Identification of Photocatalytic Alkaloids from Coptidis Rhizome by an Offline HPLC/CC/SCD Approach.

Natural products continue to be a valuable source of active metabolites; however, researchers of natural products are mostly focused on the biological effects, and their chemical utility has been less explored. Furthermore, low throughput is a bottleneck for classical natural product research. In this work, a new offline HPLC/CC/SCD (high performance liquid chromatography followed by co-crystallization and single crystal diffraction) workflow was developed that greatly expedites the discovery of active compounds from crude natural product extracts. The photoactive total alkaloids of the herbal medicine Coptidis rhizome were firstly separated by HPLC, and the individual peaks were collected. A suitable coformer was screened by adding it to the individual peak solution and observing the precipitation, which was then redissolved and used for co-crystallization. Seven new co-crystals were obtained, and all the single crystals were subjected to X-ray diffraction analysis. The molecular structures of seven alkaloids from milligrams of crude extract were resolved within three days. NDS greatly decreases the required crystallization amounts of alkaloids to the nanoscale and enables rapid stoichiometric inclusion of all the major alkaloids with full occupancy, typically without disorder, affording well-refined structures. It is noteworthy that anomalous scattering by the coformer sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. Moreover, the identified alkaloids were firstly found to be photocatalysts for the green synthesis of benzimidazoles. This study demonstrates a new and green phytochemical workflow that can greatly accelerate natural product discovery from complex samples.

Silybin B exerts protective effect on cisplatin-induced neurotoxicity by alleviating DNA damage and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Silybum marianum is a traditional Chinese medicine that has been used for treating liver disease. Silybin consisting of silybin A and silybin B, is a member of Silybum marianum, and exerts a therapeutic effect on many diseases. However, the protective effect of silybin on cisplatin-induced neurotoxicity and the stereoisomer contributing to the effect remain unknown. AIM OF THE STUDY: The present study aimed to study the effect of silybin on cisplatin-induced neuronal injury, compare the difference of protective effect between silybin A and silybin B, and the potential mechanism. MATERIALS AND METHODS: High performance liquid chromatography (HPLC) was used to separate silybin A and silybin B. X-ray crystallographic analysis in combination with experimental and calculated ECD were performed to identify the structure of silybin A and silybin B. The toxicity of the silybin or cisplatin against murine hippocampal neuronal HT22 cells was determined through MTT assay. The cell cycle and cell apoptosis were measured by PI staining and Annexin V-FITC/PI staining, respectively, and then subjected to flow cytometry. Western blot analysis was conducted to quantify the expression of proteins related to apoptosis and DNA damage. Immunofluorescence was used to evaluate the expression of DNA damage marker. In vivo experiment, the behavioral analysis was determined through pole test, swimming test and Morris water maze test. The index of superoxide dismutase (SOD), reduced glutathione (GSH), total antioxidant capacity (T-AOC) and lipid peroxidation (LPO) were examined to evaluate the antioxidant capacity in mice brain. Nissl staining and Tunel assay were used to detect the neuronal viability and apoptosis in hippocampus. RESULTS: We successfully separated and identified silybin A and silybin B. We found both silybin A and silybin B alleviated cisplatin-induced apoptosis and cell cycle arrest in HT22 cells, and silybin B was more effective. We chose silybin B for further mechanism investigation, and found silybin B alleviated DNA damage by enhancing phosphorylation of ATR and decreasing expression of γ-H2AX. In the in vivo experiment, we observed that silybin B markedly improved the behavioral abnormalities in cisplatin-treated mice, reduced LPO level while increased SOD, GSH and T-AOC in mice brain tissue. Nissl staining and Tunel assay showed that silybin B alleviated cisplatin-induced hippocampal damage. CONCLUSIONS: These results suggest that silybin B might serve as a promising drug candidate in mitigating cisplatin-induced neural injury in the brain and thereby improving the chemotherapeutic outcomes.

Chemical constituents with inhibition against TNF-α from Merrillanthus hainanensis.

Two new steroidal glycosides oxystauntoside A (1) and oxystauntoside B (2), together with sixteen known compounds (3-18) were isolated from the 95% ethanol extract of Merrillanthus hainanensis. Their structures were characterized by extensive spectroscopic analysis including NMR and mass spectra and single crystal X-ray crystallography. The absolute configuration of 1 and 2 were further determined by ECD calculations. All of these compounds were isolated from M. hainanensis for the first time. All the fractions and compounds were tested for the anti-inflammatory activity against the TNF-α factor. The ethyl acetate fraction showed the most potent inhibition (71.3%) at 10 µg/mL and compounds 5 (78.9%) and 9 (73.4%) in this fraction with both carboxyl and phenolic hydroxyl groups showed significant inhibition at 10 µM. Our study provided the first scientific report for the medicinal value of M. hainanensis.

Polyprenylated acylphloroglucinols as deubiquitinating protease USP7 inhibitors from Hypericum hookerianum.

Hookerianones A - E (1-5), five new polyprenylated acylphloroglucinols (PPAPs), along with six known ones, were isolated from the aerial parts of Hypericum hookerianum. Their structures were elucidated by analyses of MS, NMR, chiroptical properties, biogenetic pathway, and/or single crystal X-ray diffraction. A ubiquitin-rhodamine 110 assay showed that furohyperforin and hypercalin C, two representative PPAPs in this plant, inhibited more than 90% USP7 at the concentration of 10 µM.

Association between Selenium in Soil and Diabetes in Chinese Residents Aged 35-74 Years: Results from the 2010 National Survey of Chronic Diseases and Behavioral Risk Factors Surveillance.

OBJECTIVE: To explore the association between soil selenium levels and the risk of diabetes in Chinese adults aged 35-74 years. METHODS: Data for this study were derived from the China Chronic Diseases and Behavioral Risk Factors Surveillance 2010 survey. Selenium concentrations in soil were obtained from the Atlas of Soil Environmental Background Values in China. A two-level binary logistic regression model was used to determine the association between soil selenium concentrations and the risk of diabetes, with participants nested within districts/counties. RESULTS: A total of 69,332 participants aged 35-74 years, from 158 districts/counties were included in the analysis. Concentrations of selenium in soil varied greatly across the 158 districts/counties, with a median concentration of 0.219 mg/kg ( IQR: 0.185-0.248). The results showed that both Quartile 1 (0.119-0.185 mg/kg) and Quartile 4 (0.249-0.344 mg/kg) groups were positively associated with diabetes compared to a soil selenium concentration of 0.186-0.219 mg/kg (Quartile 2), crude odds ratios ( ORs) (95% CI) were 1.227 (1.003-1.502) and 1.280 (1.048-1.563). The P values were 0.045 and 0.013, for Quartile 1 and Quartile 4 groups, respectively. After adjusting for all confounding factors of interest, the Quartile 1 group became non-significant, and the Quartile 4 group had an adjusted OR (95% CI) of 1.203 (1.018-1.421) relative to the reference group (Quartile 2), the P values was 0.030. No significant results were seen for the Quartile 3 group (0.220-0.248 mg/kg) compared to the reference group. CONCLUSION: Excessive selenium concentrations in soil could increase the risk of diabetes among Chinese adults aged 35-74 years.

Anti-inflammatory constituents from Perilla frutescens on lipopolysaccharide-stimulated RAW264.7 cells.

Perilla frutescens (L.) Britt. (Lamiaceae) is a traditionally medicinal herb in East Asian countries to treat various diseases. In present study, the low-polarity constituents of the aerial parts of P. frutescens were investigated and their anti-inflammatory effect on lipopolysaccharide (LPS)-stimulated RAW264.7 cells were assayed. Three new furanoid monoterpenoids, named as frutescenones A - C (1-3), together with thirteen known compounds (4-16) were isolated and identified on the basis of extensive spectroscopic analysis and a single-crystal X-ray diffraction study. Among these components, 1 is an unusual monoterpenoid with 2,3'-bifuran skeleton, and 3 is a rare perillaketone-adenine hybrid heterodimer, while the revised NMR arrangements of 4 were reported at the first time. Furthermore, monoterpenoid 4 and alkaloid 15 showed remarkably inhibitory effect on the production of inflammatory mediator (NO) and pro-inflammatory cytokines (TNF-α and/or IL-6) in LPS-stimulated RAW264.7 cells.

[Response of Soil Enzyme Activities and Their Relationships with Physicochemical Properties to Different Aged Coastal Reclamation Areas, Eastern China].

Land reclamation transforms a tidal flat from a marine ecosystem to terrestrial ecosystem, which significantly changes the soil ecosystem process, affecting the soil enzyme activities. Soil enzyme is involved in almost all soil biochemical processes. Clarifying the relationship between soil physicochemical properties and soil enzyme activities can reveal the changes of soil quality after reclamation and provide a theoretical basis for the scientific regulation of the soil ecosystem. In this study, a total of 72 soil samples were collected from a coastal reclamation area with different years of reclamation (0, 7, 32, 40, and 63 a) in Rudong County. The changes in soil physicochemical properties and enzyme activities within different reclamation years were analyzed by classical statistical analysis, and the relationship between soil enzyme activities and physicochemical properties was analyzed using a redundancy analysis. The results showed that longterm land reclamation had significant effects on soil physicochemical properties and enzyme activities. pH and electrical conductivity showed a decreasing trend after reclamation, while the content of soil organic carbon, total nitrogen, and total phosphorus showed a trend of "rapidly accumulate-gradually consume-accumulate again" with increasing years of reclamation. Compared with the bare flat area (0 a), amylase, dehydrogenase, and acid phosphatase activity initially increased and then decreased with increasing years of reclamation, while urease and alkaline phosphatase activities were characterized by an increase-decrease-increase trend. Meanwhile, the enzyme activities within different reclamation ages were basically higher in surface soil than deep layers. Redundancy analysis revealed that the soil physicochemical properties explained 69.8% of the variation in soil enzyme activities, and an obvious relationship existed between pH, electronic conductivity, soil organic carbon, total nitrogen, total phosphorus, and soil enzyme activities (P<0.01). The order of importance of soil physicochemical properties to soil enzyme activities was as follows:total nitrogen > soil organic carbon > pH > total phosphorus > electronic conductivity.